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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03947385




Registration number
NCT03947385
Ethics application status
Date submitted
9/05/2019
Date registered
13/05/2019
Date last updated
18/11/2023

Titles & IDs
Public title
Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Scientific title
A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Secondary ID [1] 0 0
IDE196-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Uveal Melanoma 0 0
Cutaneous Melanoma 0 0
Colorectal Cancer 0 0
Other Solid Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IDE196
Treatment: Drugs - Binimetinib
Treatment: Drugs - Crizotinib

Experimental: Dose Escalation Monotherapy - IDE196 dosed orally, twice daily (BID) for each 28-day cycle

Experimental: Dose Expansion Monotherapy - RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

Experimental: Dose Escalation Binimetinib Combination - IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

Experimental: Dose Expansion Binimetinib Combination - RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Experimental: Dose Escalation Crizotinib Combination - IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Experimental: Dose Expansion Crizotinib Combination - RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Experimental: Dose Optimization Crizotinib Combination - IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Experimental: Crizotinib Monotherapy with Crossover to Combination - Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle

Experimental: Tablet PK Substudy - IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle


Treatment: Drugs: IDE196
IDE196 dosed orally, twice daily for each 28-day cycle

Treatment: Drugs: Binimetinib
Binimetinib dosed orally, twice daily for each 28-day cycle

Treatment: Drugs: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-limiting Toxicity (DLT)
Timepoint [1] 0 0
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [2] 0 0
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Timepoint [3] 0 0
Approx. 6 months
Primary outcome [4] 0 0
Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Timepoint [4] 0 0
Approx. 6 months
Primary outcome [5] 0 0
Plasma Concentrations of Crizotinib administered in combination with IDE196
Timepoint [5] 0 0
Approx. 6 months
Primary outcome [6] 0 0
Plasma Concentrations of Binimetinib administered in combination with IDE196
Timepoint [6] 0 0
Approx. 6 months
Primary outcome [7] 0 0
Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Timepoint [7] 0 0
Approx. 48 months
Primary outcome [8] 0 0
Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee
Timepoint [8] 0 0
Approx. 48 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and all combination cohorts by Blinded Independent Review Committee
Timepoint [1] 0 0
Approx. 48 months
Secondary outcome [2] 0 0
Duration of Response for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and in all combination cohorts by Blinded Independent Review Committee
Timepoint [2] 0 0
Approx. 48 months
Secondary outcome [3] 0 0
ORR by Investigator
Timepoint [3] 0 0
Approx. 48 months
Secondary outcome [4] 0 0
Duration of Response by Investigator
Timepoint [4] 0 0
Approx. 48 months
Secondary outcome [5] 0 0
Disease Control by Investigator
Timepoint [5] 0 0
Approx. 48 months
Secondary outcome [6] 0 0
Numbers of Participants with Adverse Events
Timepoint [6] 0 0
Approx. 48 months
Secondary outcome [7] 0 0
Treatment-related pharmacodynamic effect in all patients
Timepoint [7] 0 0
Approx. 48 months

Eligibility
Key inclusion criteria
- Patient must be =18 years of age

- Diagnosis of one of the following:

- MUM: Uveal melanoma with histological or cytological confirmed metastatic
disease. Or

- Non-MUM: Advanced cutaneous melanoma, colorectal cancer, or other solid tumor
that has progressed following prior standard therapies or that has no
satisfactory alternative therapies and has evidence of GNAQ/11 hotspot mutation

- Measurable disease

- Eastern Cooperative Oncology Group =1 and expected life expectancy of > 3 months

- Adequate organ function at screening

- Adequate contraceptive measures for non-sterilized male and female patients of
childbearing potential

Binimetinib Combination Additional

• Adequate cardiac function represented by left ventricular ejection fraction (LVEF) = 50%

Crizotinib Combination Additional

- Prior chemotherapy other therapies as applicable or major surgeries must have been
completed at least 4 weeks prior to initiation of crizotinib

- Patients with preexisting peripheral neuropathy can be included if it is Grade 1 or
lower, prior to initiation of crizotinib
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known symptomatic brain metastases

- Previous treatment with a PKC inhibitor

- Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors

- Adverse events from prior anti-cancer therapy that have not resolved

- Known acquired immunodeficiency syndrome (AIDS)-related illness, hepatitis B virus, or
hepatitis C virus

- Active infection requiring ongoing therapy

- Recent surgery or radiotherapy

- Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder or
defect

- Females who are pregnant or breastfeeding

- Impaired cardiac function

- Treatment with prohibited medications that cannot be discontinued prior to study entry

- For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib,
allergy to mammalian meat products and gelatin

Binimetinib Combination Additional Exclusion Criteria

- Prior treatment with a MEK inhibitor

- History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO

- History of interstitial lung disease

- History of thromboembolic or cerebrovascular events = 12 weeks prior to first dose

- Concurrent neuromuscular disorders that are associated with elevated creatine
phosphokinase (CPK)

- Uncontrolled arterial hypertension despite medical treatment

- Allergy to binimetinib or its components

- History of syncope

Crizotinib Combination Additional

- Prior therapy directly targeting ALK, MET, or ROS1

- Spinal cord compression

- History of pneumonitis or interstitial lung disease

- History of syncope

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2025
Actual
Sample size
Target
278
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
IDEAYA Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety
and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11
(GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous
melanoma, colorectal cancer, and other solid tumors.

Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics
of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose.
Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the
study.

Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of
IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet

Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and
pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine
the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2
(dose expansion) part of the study.

Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and
pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine
the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2
(dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses
may be explored in the dose optimization part of the study.

Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to
show the contribution of each study drug to anti-tumor activity.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03947385
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jasgit Sachdev, MD
Address 0 0
[email protected]
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
IDEAYA Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
+1 650 534 3616
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03947385